JP2001502326A - マトリクス金属プロテナイーゼおよびＴＡＣＥに対する阻害薬としてのβ―スルホンアミドヒドロキサム酸 - Google Patents

マトリクス金属プロテナイーゼおよびＴＡＣＥに対する阻害薬としてのβ―スルホンアミドヒドロキサム酸

Info

Publication number: JP2001502326A
Authority: JP; Japan
Prior art keywords: defined above; disease; heteroaryl; ring; aryl
Prior art date: 1996-10-16
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Ceased

Application number

JP10518424A

Other languages

English (en)

Japanese (ja)

Inventor

レビン，ジェレミー・イアン

ザスク，アリー

グ，ヤンソン

Original Assignee

アメリカン・サイアナミド・カンパニー

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1996-10-16

Filing date

1997-10-08

Publication date

2001-02-20

1997-10-08 Application filed by アメリカン・サイアナミド・カンパニー filed Critical アメリカン・サイアナミド・カンパニー

2001-02-20 Publication of JP2001502326A publication Critical patent/JP2001502326A/ja

Status Ceased legal-status Critical Current

Links

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/22—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound oxygen atoms
- C07C311/29—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound oxygen atoms having the sulfur atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C257/00—Compounds containing carboxyl groups, the doubly-bound oxygen atom of a carboxyl group being replaced by a doubly-bound nitrogen atom, this nitrogen atom not being further bound to an oxygen atom, e.g. imino-ethers, amidines
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/14—The ring being saturated

JP10518424A 1996-10-16 1997-10-08 マトリクス金属プロテナイーゼおよびＴＡＣＥに対する阻害薬としてのβ―スルホンアミドヒドロキサム酸 Ceased JP2001502326A (ja)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
US72935996A	1996-10-16	1996-10-16
US08/729,359		1996-10-16
PCT/US1997/018170 WO1998016506A1 (en)	1996-10-16	1997-10-08	Beta-sulfonamido hydroxamic acids as matrix metalloproteinase and tace inhibitors

Publications (1)

Publication Number	Publication Date
JP2001502326A true JP2001502326A (ja)	2001-02-20

Family

ID=24930685

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
JP10518424A Ceased JP2001502326A (ja)	1996-10-16	1997-10-08	マトリクス金属プロテナイーゼおよびＴＡＣＥに対する阻害薬としてのβ―スルホンアミドヒドロキサム酸

Country Status (18)

Country	Link
EP (1)	EP0934259B1 (da)
JP (1)	JP2001502326A (da)
KR (1)	KR20000049198A (da)
CN (1)	CN1105101C (da)
AR (1)	AR008676A1 (da)
AT (1)	ATE224364T1 (da)
AU (1)	AU736134B2 (da)
BR (1)	BR9712524A (da)
CA (1)	CA2268895A1 (da)
DE (1)	DE69715647T2 (da)
DK (1)	DK0934259T3 (da)
ES (1)	ES2184069T3 (da)
HK (1)	HK1020720A1 (da)
IL (1)	IL129149A (da)
NZ (1)	NZ335053A (da)
PT (1)	PT934259E (da)
WO (1)	WO1998016506A1 (da)
ZA (1)	ZA979236B (da)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
JP2011079866A (ja) *	2004-03-22	2011-04-21	Southern Research Inst	マトリックスメタロプロテイナーゼの非ペプチドインヒビター
JP2012531460A (ja) *	2009-06-30	2012-12-10	ガルデルマ・リサーチ・アンド・デヴェロップメント	新規なベンゼンスルホンアミド化合物、その合成方法、ならびに医薬および化粧品におけるその使用
JP2012531397A (ja) *	2009-06-30	2012-12-10	ガルデルマ・リサーチ・アンド・デヴェロップメント	新規なベンゼンスルホンアミド化合物、その合成方法、ならびに医学および化粧品におけるその使用

Families Citing this family (23)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
PT952148E (pt) *	1998-04-10	2004-09-30	Pfizer Prod Inc	Derivados de acido ciclobutil-ariloxiarilsulfonilamino-hidroxamico
EP1087937A1 (en)	1998-06-17	2001-04-04	Du Pont Pharmaceuticals Company	Cyclic hydroxamic acids as metalloproteinase inhibitors
US6326516B1 (en)	1999-01-27	2001-12-04	American Cyanamid Company	Acetylenic β-sulfonamido and phosphinic acid amide hydroxamic acid TACE inhibitors
US6340691B1 (en)	1999-01-27	2002-01-22	American Cyanamid Company	Alkynyl containing hydroxamic acid compounds as matrix metalloproteinase and tace inhibitors
BR0007784A (pt)	1999-01-27	2002-02-05	American Cyanamid Co	Composto, método para inibir mudanças patológicas mediadas pela enzima que converte o tnf-alfa (tace) em um mamìfero, composição farmacêutica, e, processo para preparar um composto
US6200996B1 (en)	1999-01-27	2001-03-13	American Cyanamid Company	Heteroaryl acetylenic sulfonamide and phosphinic acid amide hydroxamic acid tace inhibitors
US6753337B2 (en)	1999-01-27	2004-06-22	Wyeth Holdings Corporation	Alkynyl containing hydroxamic acid compounds as matrix metalloproteinase/tace inhibitors
US6946473B2 (en)	1999-01-27	2005-09-20	Wyeth Holdings Corporation	Preparation and use of acetylenic ortho-sulfonamido and phosphinic acid amido bicyclic heteroaryl hydroxamic acids as TACE inhibitors
US6277885B1 (en)	1999-01-27	2001-08-21	American Cyanamid Company	Acetylenic aryl sulfonamide and phosphinic acid amide hydroxamic acid TACE inhibitors
US6225311B1 (en)	1999-01-27	2001-05-01	American Cyanamid Company	Acetylenic α-amino acid-based sulfonamide hydroxamic acid tace inhibitors
US6313123B1 (en)	1999-01-27	2001-11-06	American Cyanamid Company	Acetylenic sulfonamide thiol tace inhibitors
US6762178B2 (en)	1999-01-27	2004-07-13	Wyeth Holdings Corporation	Acetylenic aryl sulfonamide and phosphinic acid amide hydroxamic acid TACE inhibitors
WO2000046189A1 (fr) *	1999-02-02	2000-08-10	Shionogi & Co., Ltd.	Derives de la sulfonamide a structures cycliques
KR100780989B1 (ko) *	2000-05-23	2007-11-29	오스모닉스 인코포레이티드	개질된 술폰아미드 중합체
JP2005507937A (ja)	2001-11-01	2005-03-24	ワイス・ホールディングズ・コーポレイション	マトリックスメタロプロテイナーゼおよびｔａｃｅ阻害剤としてのアレンアリールスルホンアミドヒドロキサム酸
US7491718B2 (en)	2002-10-08	2009-02-17	Abbott Laboratories	Sulfonamides having antiangiogenic and anticancer activity
US20040157836A1 (en) *	2002-10-08	2004-08-12	Comess Kenneth M.	Sulfonamides having antiangiogenic and anticancer activity
US7199155B2 (en)	2002-12-23	2007-04-03	Wyeth Holdings Corporation	Acetylenic aryl sulfonate hydroxamic acid TACE and matrix metalloproteinase inhibitors
US20140275108A1 (en)	2013-03-15	2014-09-18	Galderma Research & Development	Novel benzenesulfonamide compounds, method for synthesizing same, and use thereof in medicine as well as in cosmetics
IL237852A0 (en)	2015-03-19	2016-03-24	Yeda Res & Dev	Antibodies against amphigoline, medical preparations containing them and their use
WO2017117130A1 (en)	2015-12-28	2017-07-06	The United States Of America, As Represented By The Secretary, Department Of Health & Human Services	Methods for inhibiting human immunodeficiency virus (hiv) release from infected cells
EP3199534B1 (en)	2016-02-01	2018-09-05	Galderma Research & Development	Benzenesulfonamide compounds, method for synthesizing same, and use thereof in medicine and cosmetics
BR112021006407A8 (pt)	2018-10-04	2022-12-06	Inst Nat Sante Rech Med	uso de inibidores do egfr para ceratodermas

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US5455258A (en) *	1993-01-06	1995-10-03	Ciba-Geigy Corporation	Arylsulfonamido-substituted hydroxamic acids
WO1994022309A1 (en) *	1993-04-07	1994-10-13	Glycomed Incorporated	Synthetic matrix metalloprotease inhibitors and uses thereof
US5672598A (en) *	1995-03-21	1997-09-30	The Procter & Gamble Company	Lactam-containing hydroxamic acids

1997
- 1997-10-08 JP JP10518424A patent/JP2001502326A/ja not_active Ceased
- 1997-10-08 DE DE69715647T patent/DE69715647T2/de not_active Expired - Fee Related
- 1997-10-08 IL IL12914997A patent/IL129149A/xx not_active IP Right Cessation
- 1997-10-08 DK DK97912674T patent/DK0934259T3/da active
- 1997-10-08 BR BR9712524-5A patent/BR9712524A/pt not_active Application Discontinuation
- 1997-10-08 NZ NZ335053A patent/NZ335053A/xx unknown
- 1997-10-08 KR KR1019990703296A patent/KR20000049198A/ko active IP Right Grant
- 1997-10-08 CN CN97180606A patent/CN1105101C/zh not_active Expired - Fee Related
- 1997-10-08 AU AU49790/97A patent/AU736134B2/en not_active Ceased
- 1997-10-08 PT PT97912674T patent/PT934259E/pt unknown
- 1997-10-08 ES ES97912674T patent/ES2184069T3/es not_active Expired - Lifetime
- 1997-10-08 AT AT97912674T patent/ATE224364T1/de not_active IP Right Cessation
- 1997-10-08 WO PCT/US1997/018170 patent/WO1998016506A1/en active IP Right Grant
- 1997-10-08 CA CA002268895A patent/CA2268895A1/en not_active Abandoned
- 1997-10-08 EP EP97912674A patent/EP0934259B1/en not_active Expired - Lifetime
- 1997-10-15 ZA ZA9709236A patent/ZA979236B/xx unknown
- 1997-10-15 AR ARP970104748A patent/AR008676A1/es not_active Application Discontinuation
1999
- 1999-12-11 HK HK99105839A patent/HK1020720A1/xx not_active IP Right Cessation

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
JP2011079866A (ja) *	2004-03-22	2011-04-21	Southern Research Inst	マトリックスメタロプロテイナーゼの非ペプチドインヒビター
JP2012531460A (ja) *	2009-06-30	2012-12-10	ガルデルマ・リサーチ・アンド・デヴェロップメント	新規なベンゼンスルホンアミド化合物、その合成方法、ならびに医薬および化粧品におけるその使用
JP2012531397A (ja) *	2009-06-30	2012-12-10	ガルデルマ・リサーチ・アンド・デヴェロップメント	新規なベンゼンスルホンアミド化合物、その合成方法、ならびに医学および化粧品におけるその使用
US8980897B2 (en)	2009-06-30	2015-03-17	Galderma Research & Development	Benzenesulfonamide compounds, method for synthesizing same, and use thereof in medicine as well as in cosmetics
US9365529B2 (en)	2009-06-30	2016-06-14	Galderma Research & Devlopment	Benzenesulfonamide compounds, method for synthesizing same, and use thereof in medicine as well as in cosmetics

Also Published As

Publication number	Publication date
ATE224364T1 (de)	2002-10-15
EP0934259B1 (en)	2002-09-18
WO1998016506A1 (en)	1998-04-23
ZA979236B (en)	1999-07-15
CN1105101C (zh)	2003-04-09
AU736134B2 (en)	2001-07-26
IL129149A0 (en)	2000-02-17
KR20000049198A (ko)	2000-07-25
NZ335053A (en)	2000-10-27
DE69715647D1 (en)	2002-10-24
DE69715647T2 (de)	2003-02-20
DK0934259T3 (da)	2003-01-27
ES2184069T3 (es)	2003-04-01
CN1240424A (zh)	2000-01-05
AU4979097A (en)	1998-05-11
IL129149A (en)	2003-10-31
BR9712524A (pt)	1999-10-19
EP0934259A1 (en)	1999-08-11
PT934259E (pt)	2003-01-31
AR008676A1 (es)	2000-02-09
CA2268895A1 (en)	1998-04-23
HK1020720A1 (en)	2000-05-19

Legal Events

Date	Code	Title	Description
2004-09-16	A621	Written request for application examination	Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20040825
2007-10-16	A131	Notification of reasons for refusal	Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20071016
2008-04-03	A313	Final decision of rejection without a dissenting response from the applicant	Free format text: JAPANESE INTERMEDIATE CODE: A313 Effective date: 20080313
2008-04-22	A02	Decision of refusal	Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20080422

Publication	Publication Date	Title
JP2001502326A (ja)	2001-02-20	マトリクス金属プロテナイーゼおよびＴＡＣＥに対する阻害薬としてのβ―スルホンアミドヒドロキサム酸
JP2001503037A (ja)	2001-03-06	マトリクス金属プロテナイーゼおよびｔａｃｅに対する阻害薬としてのオルト―スルホンアミドヘテロアリールヒドロキサム酸の製造および使用
JP2001504809A (ja)	2001-04-10	マトリクス金属プロテナイーゼおよびｔａｃｅに対する阻害薬としてのオルト―スルホンアミドアリールヒドロキサム酸の製造および使用
RU2073676C1 (ru)	1997-02-20	5-фтор-2-01([(4-циклопропилметокси-2-пиридинил)метил] сульфинил01)-1h-бензимидазол или его физиологически приемлемая соль, фармкомпозиция на его основе и промежуточные соединения
US6197795B1 (en)	2001-03-06	Preparation and use of ortho-sulfonamido heteroaryl hydroxamic acids as matrix metalloproteinase and tace inhibitors
JP2002503720A (ja)	2002-02-05	マトリックス分解メタロプロテイナーゼを阻害するスルホニルアミノ誘導体
US10604513B2 (en)	2020-03-31	Pyridone derivative comprising heteroatomic ring butane substituent, for treating fibrosis and inflammatory diseases
JP5329656B2 (ja)	2013-10-30	イミダゾリジン誘導体
JP2002538146A (ja)	2002-11-12	ジヘテロ−置換メタロプロテアーゼ阻害剤
DE60012303T2 (de)	2005-07-28	Alkinylische hydroxamsäureverbindungen als tace inhibitoren
US6326516B1 (en)	2001-12-04	Acetylenic β-sulfonamido and phosphinic acid amide hydroxamic acid TACE inhibitors
US6200996B1 (en)	2001-03-13	Heteroaryl acetylenic sulfonamide and phosphinic acid amide hydroxamic acid tace inhibitors
DE60012302T2 (de)	2005-08-04	Acetylenische arylsulfonamid- und phosphinsäureamid-hydroxamsäure-derivate als tace inhibitoren
EP0430459A1 (en)	1991-06-05	Tetrahydronaphthalene derivatives and preparation thereof
US20010051614A1 (en)	2001-12-13	Preparation and use of ortho-sulfonamido heteroaryl hydroxamic acids as matrix metalloproteinase and TACE inhibitors
KR20010089617A (ko)	2001-10-06	아세틸렌계 베타-설폰아미도 및 포스핀산 아미드하이드록삼산 티에이씨이 억제제
JP2003524000A (ja)	2003-08-12	オルト−スルホンアミドアリールヒドロキサム酸、それらの製造方法およびマトリックスメタロプロテイナーゼ阻害薬としてのそれらの使用
CN101252838A (zh)	2008-08-27	新型含异羟肟酸的氨基酸衍生物
JP2002520401A (ja)	2002-07-09	ピペラジノン誘導体及びその利用
JP2881688B2 (ja)	1999-04-12	スルホンアミド誘導体
JP2936324B2 (ja)	1999-08-23	スルホンアミド誘導体
JP2007530424A (ja)	2007-11-01	新規Ｎ−ヒドロキシ−４−（３−フェニル−５−メチル−イソオキサゾール−４−ｙｌ）−ベンゼンスルホンアミドの溶媒和物
CZ20012708A3 (cs)	2002-04-17	Heteroarylové acetylenické sulfonamidohydroxamové a fosfinamidohydroxamové kyseliny jako inhibitory TACE
TW389750B (en)	2000-05-11	<beta> -sulfonamido hydroxamic acids, its pharmaceutical composition and use as matrix metalloproteinase and TACE inhibitors
US20020188132A1 (en)	2002-12-12	Heteroaryl acetylenic sulfonamide and phosphinic acid amide hydroxamic acid TACE inhibitors